The International Clinical Trials Registry Platform ( ICTRP ) is a platform for the registration of clinical trials operated by the World Health Organization .
88-637: The ICTRP combines data from multiple cooperating clinical trials registries to generate a global view of clinical trials worldwide, with a search portal that allows access to the entire dataset. It requires a minimum standard set of database fields, the WHO Trial Registration Data Set, to be present for a trial to be registered. All entries are given a Universal Trial Number (UTN) that identifies them uniquely. The organization has sought to assist various national governments in establishing their own clinical trials databases. It combines data from
176-602: A clinical trials registry. The World Health Organization has begun the push for clinical trial registration with the initiation of the International Clinical Trials Registry Platform . There has also been action from the pharmaceutical industry, which released plans to make clinical trial data more transparent and publicly available. Released in October 2008, the revised Declaration of Helsinki , states that "Every clinical trial must be registered in
264-415: A dietary supplement of an acidic quality in the experiment after two months at sea, when the ship was already afflicted with scurvy. He divided twelve scorbutic sailors into six groups of two. They all received the same diet but, in addition, group one was given a quart of cider daily, group two twenty-five drops of elixir of vitriol ( sulfuric acid ), group three six spoonfuls of vinegar , group four half
352-461: A different purpose to construct focus on identifying a specific effect. Clinical trials involving new drugs are commonly classified into five phases. Each phase of the drug approval process is treated as a separate clinical trial. The drug development process will normally proceed through phases I–IV over many years, frequently involving a decade or longer. If the drug successfully passes through phases I, II, and III, it will usually be approved by
440-418: A false sense of credibility to research studies and analyses ( Devezer et al., 2020 ; McPhetres, 2020 ; Pham & Oh, 2020 ; Szollosi et al., 2020 ). Consistent with this view, there is some evidence that researchers view registered reports as being more credible than standard reports on a range of dimensions ( Soderberg et al., 2020 ; see also Field et al., 2020 for inconclusive evidence), although it
528-419: A landmark study carried out in collaboration with Richard Doll on the correlation between smoking and lung cancer . They carried out a case-control study in 1950, which compared lung cancer patients with matched control and also began a sustained long-term prospective study into the broader issue of smoking and health, which involved studying the smoking habits and health of more than 30,000 doctors over
616-546: A national regulatory authority approves marketing of the innovation. Similarly to drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket approval . Device trials may compare a new device to an established therapy, or may compare similar devices to each other. An example of the former in the field of vascular surgery is the Open versus Endovascular Repair (OVER trial) for
704-434: A panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type(s) of patients might benefit. If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study. During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment(s) and collect data on
792-492: A period of several years. His certificate for election to the Royal Society called him "... the leader in the development in medicine of the precise experimental methods now used nationally and internationally in the evaluation of new therapeutic and prophylactic agents ." International clinical trials day is celebrated on 20 May. The acronyms used in the titling of clinical trials are often contrived, and have been
880-465: A pint of seawater, group five received two oranges and one lemon , and the last group a spicy paste plus a drink of barley water . The treatment of group five stopped after six days when they ran out of fruit, but by then one sailor was fit for duty while the other had almost recovered. Apart from that, only group one also showed some effect of its treatment. Each year, May 20 is celebrated as Clinical Trials Day in honor of Lind's research. After 1750
968-412: A placebo to a person suffering from a disease may be unethical, "active comparator" (also known as "active control") trials may be conducted instead. In trials with an active control group, subjects are given either the experimental treatment or a previously approved treatment with known effectiveness. In other cases, sponsors may conduct an active comparator trial to establish an efficacy claim relative to
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#17328986245731056-428: A publicly accessible database before recruitment of the first subject." The World Health Organization maintains an international registry portal at http://apps.who.int/trialsearch/ . WHO states that the international registry's mission is "to ensure that a complete view of research is accessible to all those involved in health care decision making. This will improve research transparency and will ultimately strengthen
1144-624: A registered report, authors create a study proposal that includes theoretical and empirical background, research questions/hypotheses, and pilot data (if available). Upon submission, this proposal will then be reviewed prior to data collection, and if accepted, the paper resulting from this peer-reviewed procedure will be published, regardless of the study outcomes.” Note that only a very small proportion of academic journals in psychology and neurosciences explicitly stated that they welcome submissions of replication studies in their aim and scope or instructions to authors. This phenomenon does not encourage
1232-773: A role in clinical trials. While working for the Rothamsted experimental station in the field of agriculture, Fisher developed his Principles of experimental design in the 1920s as an accurate methodology for the proper design of experiments. Among his major ideas include the importance of randomization —the random assignment of individuals to different groups for the experiment; replication —to reduce uncertainty , measurements should be repeated and experiments replicated to identify sources of variation; blocking —to arrange experimental units into groups of units that are similar to each other, and thus reducing irrelevant sources of variation; use of factorial experiments —efficient at evaluating
1320-420: A similar cutoff age) are often excluded from trials because their greater health issues and drug use complicate data interpretation, and because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are also frequently excluded. Pregnant women are often excluded due to potential risks to the fetus . The sponsor designs the trial in coordination with
1408-540: A single disease entering and leaving the platform), and basket trial (one medical product for multiple diseases or disease subtypes). Genetic testing enables researchers to group patients according to their genetic profile, deliver drugs based on that profile to that group and compare the results. Multiple companies can participate, each bringing a different drug. The first such approach targets squamous cell cancer , which includes varying genetic disruptions from patient to patient. Amgen, AstraZeneca and Pfizer are involved,
1496-491: A single research center or multiple centers , in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug, and the complete trial process to approval may require 7–15 years. The sponsor may be a governmental organization or a pharmaceutical , biotechnology or medical-device company. Certain functions necessary to
1584-406: A study requires careful deliberation about the study's hypotheses, research design and statistical analyses. This depends on the use of pre-registration templates that provides detailed guidance on what to include and why ( Bowman et al., 2016 ; Haven & Van Grootel, 2019 ; Van den Akker et al., 2021 ). Many pre-registration template stress the importance of a power analysis but not only stress
1672-423: A treatment can have nonspecific effects. These are controlled for by the inclusion of patients who receive only a placebo. Subjects are assigned randomly without informing them to which group they belonged. Many trials are doubled-blinded so that researchers do not know to which group a subject is assigned. Assigning a subject to a placebo group can pose an ethical problem if it violates his or her right to receive
1760-568: Is a platform which catalogs registered clinical trials. ClinicalTrials.gov , run by the United States National Library of Medicine (NLM) was the first online registry for clinical trials, and remains the largest and most widely used. In addition to combating bias, clinical trial registries serve to increase transparency and access to clinical trials for the public. Clinical trials registries are often searchable (e.g. by disease/indication, drug, location, etc.). Trials are registered by
1848-561: Is also supposed to be “a plan, not a prison” ( Dehaven, 2017 ). However, critics counterargue that, if preregistration is only supposed to be a plan, and not a prison, then researchers should feel free to deviate from that plan and undertake exploratory analyses without fearing accusations of low research credibility due to circular reasoning and inappropriate research practices such as p -hacking and unreported multiple testing that leads to inflated familywise error rates (e.g., Navarro, 2020 ). Again, they have pointed out that preregistration
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#17328986245731936-431: Is not necessary to address such concerns. For example, concerns about p -hacking and unreported multiple testing can be addressed if researchers engage in other open science practices, such as (a) open data and research materials and (b) robustness or multiverse analyses (Rubin, 2020 ; Steegen et al., 2016 ; for several other approaches, see Srivastava, 2018 ). Finally, and more fundamentally, critics have argued that
2024-413: Is not useful to identify or justify deviations from preregistered plans when those plans do not reflect high quality theory and research practice . As Rubin (2020) explained, “we should be more interested in the rationale for the current method and analyses than in the rationale for historical changes that have led up to the current method and analyses” (pp. 378–379). In addition, pre-registering
2112-420: Is researcher and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and compliment their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using a service. They can also help to make
2200-514: Is similar, although it may not require the registration of a study's analysis protocol. Finally, registered reports include the peer review and in principle acceptance of a study protocol prior to data collection. Preregistration can have a number of different goals, including (a) facilitating and documenting research plans, (b) identifying and reducing questionable research practices and researcher biases, (c) distinguishing between confirmatory and exploratory analyses, (d) transparently evaluating
2288-420: Is still new in preclinical research. A large part of preclinical and basic biomedical research relies on animal experiments. The non-publication of results gained from animal experiments not only distorts the state of research by reinforcing the publication bias, it further represents an ethical issue. Preregistration is discussed as a measure that could counteract this problem. Following registries are suited for
2376-399: Is the practice of documenting clinical trials before they are performed in a clinical trials registry so as to combat publication bias and selective reporting . Registration of clinical trials is required in some countries and is increasingly being standardized. Some top medical journals will only publish the results of trials that have been pre-registered. A clinical trials registry
2464-514: Is then posted on a publicly available website such as the Open Science Framework or AsPredicted . The preregistered study is then conducted, and a report of the study and its results are submitted for publication together with access to the preregistration document. This preregistration approach allows peer reviewers and subsequent readers to cross-reference the preregistration document with the published research article in order to identify
2552-704: Is to improve the transparency of reported hypothesis tests, which allows readers to evaluate the extent to which decisions during the data analysis were pre-planned (maintaining statistical error control) or data-driven (increasing the Type 1 or Type 2 error rate). Meta-scientific research has revealed additional benefits. Researchers indicate preregistering a study leads to a more carefully thought through research hypothesis, experimental design, and statistical analysis. In addition, preregistration has been shown to encourage better learning of Open Science concepts and students felt that they understood their dissertation and it improved
2640-776: Is unclear whether this represents a "false" sense of credibility due to pre-existing positive community attitudes about preregistration or a genuine causal effect of registered reports on quality of research. Clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines , drugs , dietary choices , dietary supplements , and medical devices ) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in
2728-483: Is working toward "achieving consensus on both the minimal and the optimal operating standards for trial registration". For many years, scientists and others have worried about reporting biases such that negative or null results from initiated clinical trials may be less likely to be published than positive results, thus skewing the literature and our understanding of how well interventions work. This worry has been international and written about for over 50 years. One of
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2816-489: The FDA Modernization Act of 1997 (Food and Drug Administration Modernization Act of 1997. Pub L No. 105-115, §113 Stat 2296), but the law provided neither funding nor a mechanism of enforcement. In addition, the law required that ClinicalTrials.gov only include trials of serious and life-threatening diseases. Then, two events occurred in 2004 that increased public awareness of the problems of reporting bias. First,
2904-547: The Therapeutic Trials Committee to advise and assist in the arrangement of properly controlled clinical trials on new products that seem likely on experimental grounds to have value in the treatment of disease. The first randomised curative trial was carried out at the MRC Tuberculosis Research Unit by Sir Geoffrey Marshall (1887–1982). The trial, carried out between 1946 and 1947, aimed to test
2992-409: The cohort study and the case-control study , provide less compelling evidence than the randomized controlled trial. In observational studies, the investigators retrospectively assess associations between the treatments given to participants and their health status, with potential for considerable errors in design and interpretation. A randomized controlled trial can provide compelling evidence that
3080-463: The UK also follow ICH guidelines. Journals such as Trials , encourage investigators to publish their protocols. Clinical trials recruit study subjects to sign a document representing their " informed consent ". The document includes details such as its purpose, duration, required procedures, risks, potential benefits, key contacts and institutional requirements. The participant then decides whether to sign
3168-412: The ability of a trial to detect a difference of a particular size (or larger) between the treatment and control groups. For example, a trial of a lipid -lowering drug versus placebo with 100 patients in each group might have a power of 0.90 to detect a difference between placebo and trial groups receiving dosage of 10 mg/dL or more, but only 0.70 to detect a difference of 6 mg/dL. Merely giving
3256-454: The active comparator instead of the placebo in labeling . A master protocol includes multiple substudies, which may have different objectives and involve coordinated efforts to evaluate one or more medical products in one or more diseases or conditions within the overall study structure. Trials that could develop a master protocol include the umbrella trial (multiple medical products for a single disease), platform trial (multiple products for
3344-568: The catastrophic result of Anson 's circumnavigation attracted much attention in Europe; out of 1900 men, 1400 had died, most of them allegedly from having contracted scurvy. John Woodall , an English military surgeon of the British East India Company , had recommended the consumption of citrus fruit from the 17th century, but their use did not become widespread. Lind conducted the first systematic clinical trial in 1747. He included
3432-483: The clarity of the manuscript writing, promoted rigour and were more likely to avoid questionable research practices. In addition, it becomes a tool that can supervisors can use to shape students to combat any questionable research practices. A 2024 study in the Journal of Political Economy: Microeconomics preregistration in economics journals found that preregistration did not reduce p-hacking and publication bias, unless
3520-407: The clinical trial to follow. There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy", or "effectiveness"; and to learn whether they are safe enough, called "safety". Neither is an absolute criterion; both safety and efficacy are evaluated relative to how the treatment is intended to be used, what other treatments are available, and the severity of
3608-553: The conclusions follow from the data. Because studies are accepted for publication regardless of whether the results are statistically significant Registered Reports prevent publication bias. Meta-scientific research has shown that the percentage of non-significant results in Registered Reports is substantially higher than in standard publications. Preregistration can be used in relation to a variety of different research designs and methods, including: Clinical trial registration
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3696-509: The country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies , and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve
3784-549: The discipline began to take its modern shape. The English doctor John Haygarth demonstrated the importance of a control group for the correct identification of the placebo effect in his celebrated study of the ineffective remedy called Perkin's tractors . Further work in that direction was carried out by the eminent physician Sir William Gull, 1st Baronet in the 1860s. Frederick Akbar Mahomed (d. 1884), who worked at Guy's Hospital in London , made substantial contributions to
3872-501: The disease or condition. The benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care and are used for a life-threatening condition. In the US the elderly constitute 14% of the population, while they consume over one-third of drugs. People over 55 (or
3960-425: The distinction between confirmatory and exploratory analyses is unclear and/or irrelevant ( Devezer et al., 2020 ; Rubin, 2020 ; Szollosi & Donkin, 2019 ), and that concerns about inflated familywise error rates are unjustified when those error rates refer to abstract, atheoretical studywise hypotheses that are not being tested (Rubin, 2020 , 2021 ; Szollosi et al., 2020 ). There are also concerns about
4048-562: The document. The document is not a contract, as the participant can withdraw at any time without penalty. Informed consent is a legal process in which a recruit is instructed about key facts before deciding whether to participate. Researchers explain the details of the study in terms the subject can understand. The information is presented in the subject's native language. Generally, children cannot autonomously provide informed consent, but depending on their age and other factors, may be required to provide informed assent. In any clinical trial,
4136-465: The double standard were systematic reviewers, those who summarize what is known from clinical trials. If the literature is skewed, then the results of a systematic review are also likely to be skewed, possibly favoring the test intervention when in fact the accumulated data do not show this, if all data were made public. ClinicalTrials.gov was originally developed largely as a result of breast cancer consumer lobbying, which led to authorizing language in
4224-450: The editorial staff will be asking for replication of studies with surprising findings from examinations using small sample sizes before allowing the manuscripts to be published. Nature Human Behaviour has adopted the registered report format, as it “shift[s] the emphasis from the results of research to the questions that guide the research and the methods used to answer them”. European Journal of Personality defines this format: “In
4312-412: The effects and possible interactions of several independent factors. Of these, blocking and factorial design are seldom applied in clinical trials, because the experimental units are human subjects and there is typically only one independent intervention: the treatment. The British Medical Research Council officially recognized the importance of clinical trials from the 1930s. The council established
4400-492: The efficacy of the chemical streptomycin for curing pulmonary tuberculosis . The trial was both double-blind and placebo-controlled . The methodology of clinical trials was further developed by Sir Austin Bradford Hill , who had been involved in the streptomycin trials. From the 1920s, Hill applied statistics to medicine, attending the lectures of renowned mathematician Karl Pearson , among others. He became famous for
4488-401: The findings is provisionally guaranteed (in principle acceptance). The proposed study is then performed, and the research report is submitted for Stage 2 peer review. Stage 2 peer review confirms that the actual research methods are consistent with the preregistered protocol, that quality thresholds are met (e.g., manipulation checks confirm the validity of the experimental manipulation), and that
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#17328986245734576-421: The first time they have worked together in a late-stage trial. Patients whose genomic profiles do not match any of the trial drugs receive a drug designed to stimulate the immune system to attack cancer. A clinical trial protocol is a document used to define and manage the trial. It is prepared by a panel of experts. All study investigators are expected to strictly observe the protocol. The protocol describes
4664-423: The following primary registries and data providers: This medical article is a stub . You can help Misplaced Pages by expanding it . This database -related article is a stub . You can help Misplaced Pages by expanding it . Clinical trials registry Preregistration is the practice of registering the hypotheses, methods, or analyses of a scientific study before it is conducted. Clinical trial registration
4752-502: The former has a power analysis and higher sample size than the latter but other than that they do not seem to prevent p-hacking and HARKing, as both the proportion of positive results and effect sizes are similar between preregistered and non-preregistered studies ( Van den Akker et al., 2023 ). In addition, a survey of 27 preregistered studies found that researchers deviated from their preregistered plans in all cases ( Claesen et al., 2019 ). The most frequent deviations were with regards to
4840-404: The importance of why the methodology was used. Additionally to the concerns raised about its practical implementation in quantitative research, critics have also argued that preregistration is less applicable, or even unsuitable, for qualitative research. Pre-registration imposes rigidity, limiting researchers' ability to adapt to emerging data and evolving contexts, which are essential to capturing
4928-418: The intervention's efficacy was generally lacking. For instance, Lady Mary Wortley Montagu , who campaigned for the introduction of inoculation (then called variolation) to prevent smallpox , arranged for seven prisoners who had been sentenced to death to undergo variolation in exchange for their life. Although they survived and did not contract smallpox, there was no control group to assess whether this result
5016-410: The national regulatory authority for use in the general population. Phase IV trials are performed after the newly approved drug, diagnostic or device is marketed, providing assessment about risks, benefits, or best uses. A fundamental distinction in evidence-based practice is between observational studies and randomized controlled trials . Types of observational studies in epidemiology , such as
5104-408: The number of subjects, also called the sample size, has a large impact on the ability to reliably detect and measure the effects of the intervention. This ability is described as its " power ", which must be calculated before initiating a study to figure out if the study is worth its costs. In general, a larger sample size increases the statistical power, also the cost. The statistical power estimates
5192-709: The observed data ( Nosek et al., 2018 , p. 2600). However, critics have argued that preregistration is not necessary to identify circular reasoning during exploratory analyses ( Rubin, 2020 ). Circular reasoning can be identified by analysing the reasoning per se without needing to know whether that reasoning was preregistered. Critics have also noted that the idea that preregistration improves research credibility may deter researchers from undertaking non-preregistered exploratory analyses ( Coffman & Niederle, 2015 ; see also Collins et al., 2021, Study 1 ). In response, preregistration advocates have stressed that exploratory analyses are permitted in preregistered studies, and that
5280-477: The pharmaceutical, biotech or medical device company (Sponsor) or by the hospital or foundation which is sponsoring the study, or by another organization, such as a contract research organization (CRO) which is running the study. There has been a push from governments and international organizations, especially since 2005, to make clinical trial information more widely available and to standardize registries and processes of registering. The World Health Organization
5368-542: The planned sample size, exclusion criteria, and statistical model. Hence, what were intended as preregistered confirmatory tests ended up as unplanned exploratory tests. Again, preregistration advocates argue that deviations from preregistered plans are acceptable as long as they are reported transparently and justified. They also point out that even vague preregistrations help to reduce researcher degrees of freedom and make any residual flexibility transparent ( Simmons et al., 2021, p. 180 ). However, critics have argued that it
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#17328986245735456-588: The practical implementation of preregistration. Many preregistered protocols leave plenty of room for p -hacking ( Bakker et al., 2020 ; Heirene et al., 2021 ; Ikeda et al., 2019 ; Singh et al., 2021 ; Van den Akker et al., 2023 ), and researchers rarely follow the exact research methods and analyses that they preregister ( Abrams et al., 2020 ; Claesen et al., 2019 ; Heirene et al., 2021 ; see also Boghdadly et al., 2018 ; Singh et al., 2021 ; Sun et al., 2019 ). For example, pre-registered studies are only of higher quality than non-pre-registered studies if
5544-596: The practice of preregistering studies has gained prominence to mitigate to some of the issues that are thought to underlie the replication crisis . In the standard preregistration format, researchers prepare a research protocol document prior to conducting their research. Ideally, this document indicates the research hypotheses, sampling procedure, sample size, research design, testing conditions, stimuli, measures, data coding and aggregation method, criteria for data exclusions, and statistical analyses, including potential variations on those analyses. This preregistration document
5632-434: The preregistration of preclinical studies. Over 200 journals offer a registered reports option ( Centre for Open Science, 2019 ), and the number of journals that are adopting registered reports is approximately doubling each year ( Chambers et al., 2019 ). Psychological Science has encouraged the preregistration of studies and the reporting of effect sizes and confidence intervals. The editor-in-chief also noted that
5720-678: The preregistration was accompanied by a preanalysis plan. Proponents of preregistration have argued that it is "a method to increase the credibility of published results" ( Nosek & Lakens, 2014 ), that it "makes your science better by increasing the credibility of your results" ( Centre for Open Science ), and that it "improves the interpretability and credibility of research findings" ( Nosek et al., 2018 , p. 2605). This argument assumes that non-preregistered exploratory analyses are less "credible" and/or "interpretable" than preregistered confirmatory analyses because they may involve "circular reasoning" in which post hoc hypotheses are based on
5808-510: The presence of any undisclosed deviations of the preregistration. Deviations from the preregistration are possible and common in practice, but they should be transparently reported, and the consequences for the severity of the test should be evaluated. The registered report format requires authors to submit a description of the study methods and analyses prior to data collection. Once the theoretical introduction, method, and analysis plan has been peer reviewed (Stage 1 peer review), publication of
5896-582: The process of clinical trials, where "he separated chronic nephritis with secondary hypertension from what we now term essential hypertension . He also founded the Collective Investigation Record for the British Medical Association ; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials." Ideas of Sir Ronald A. Fisher still play
5984-460: The proposals to address this potential bias was a comprehensive register of initiated clinical trials that would inform the public which trials had been started. Ethical issues were those that seemed to interest the public most, as trialists (including those with potential commercial gain) benefited from those who enrolled in trials, but were not required to “give back,” telling the public what they had learned. Those who were particularly concerned by
6072-477: The reporting or even attempt on replication studies. Overall, the number of participating journals is increasing, as indicated by the Center for Open Science , which maintains a list of journals encouraging the submission of registered reports. Several articles have outlined the rationale for preregistration (e.g., Lakens, 2019 ; Nosek et al., 2018 ; Wagenmakers et al., 2012 ). The primary goal of preregistration
6160-418: The reporting standards of their registry. Worldwide, there is growing number of registries. A 2013 study identified the following top five registries (numbers updated as of August 2013): Similar to clinical research, preregistration can help to improve transparency and quality of research data in preclinical research. In contrast to clinical research where preregistration is mandatory for vast parts it
6248-407: The research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in plain language that is clear to the wider society and the specific groups it is most relevant for. Although early medical experimentation was performed often, the use of a control group to provide an accurate comparison for the demonstration of
6336-413: The results of these analyses retain some value vis-a-vis hypothesis generation rather than hypothesis testing. Preregistration merely makes the distinction between confirmatory and exploratory research clearer ( Nosek et al., 2018 ; Nosek & Lakens, 2014 ; Wagenmakers et al., 2012 ). Hence, although preregistraton is supposed to reduce researcher degrees of freedom during the data analysis stage, it
6424-430: The richness of participants' lived experiences ( Souza-Neto & Moyle, 2025 ). Additionally, it conflicts with the inductive and flexible nature of theory-building in qualitative research, constraining the exploratory approach that is central to this methodology ( Souza-Neto & Moyle, 2025 ). Finally, some commentators have argued that, under some circumstances, preregistration may actually harm science by providing
6512-418: The safety and relative effectiveness of a medication or device: While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a placebo . Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol . The protocol is the trial's "operating manual" and ensures all researchers perform
6600-494: The scientific rationale, objective(s), design, methodology, statistical considerations and organization of the planned trial. Details of the trial are provided in documents referenced in the protocol, such as an investigator's brochure . The protocol contains a precise study plan to assure safety and health of the trial subjects and to provide an exact template for trial conduct by investigators. This allows data to be combined across all investigators/sites. The protocol also informs
6688-399: The severity of hypothesis tests, and, in the case of Registered Reports, (e) facilitating results-blind peer review, and (f) reducing publication bias. A number of research practices such as p-hacking , publication bias , data dredging , inappropriate forms of post hoc analysis , and HARKing may increase the probability of incorrect claims. Although the idea of preregistration is old,
6776-550: The study administrators (often a contract research organization ). The format and content of clinical trial protocols sponsored by pharmaceutical, biotechnology or medical device companies in the United States, European Union, or Japan have been standardized to follow Good Clinical Practice guidance issued by the International Conference on Harmonisation (ICH). Regulatory authorities in Canada , China , South Korea , and
6864-832: The study treatment causes an effect on human health. Some Phase II and most Phase III drug trials are designed as randomized, double-blind , and placebo -controlled. Clinical studies having small numbers of subjects may be "sponsored" by single researchers or a small group of researchers, and are designed to test simple questions or feasibility to expand the research for a more comprehensive randomized controlled trial. Clinical studies can be "sponsored" (financed and organized) by academic institutions, pharmaceutical companies, government entities and even private groups. Trials are conducted for new drugs, biotechnology, diagnostic assays or medical devices to determine their safety and efficacy prior to being submitted for regulatory review that would determine market approval. In cases where giving
6952-456: The subject of derision. Clinical trials are classified by the research objective created by the investigators. Trials are classified by their purpose. After approval for human research is granted to the trial sponsor, the U.S. Food and Drug Administration (FDA) organizes and monitors the results of trials according to type: Clinical trials are conducted typically in four phases, with each phase using different numbers of subjects and having
7040-430: The subjects' health for a defined time period. Data include measurements such as vital signs , concentration of the study drug in the blood or tissues, changes to symptoms, and whether improvement or worsening of the condition targeted by the study drug occurs. The researchers send the data to the trial sponsor, who then analyzes the pooled data using statistical tests . Examples of clinical trial goals include assessing
7128-443: The surgical setting, case-controlled studies will be replaced. Besides being participants in a clinical trial, members of the public can be actively collaborate with researchers in designing and conducting clinical research . This is known as patient and public involvement (PPI). Public involvement involves a working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what
7216-464: The then-New York State Attorney General Eliot Spitzer sued GlaxoSmithKline (GSK) because they had failed to reveal results from trials showing that certain antidepressants might be harmful. Shortly thereafter, the International Committee of Medical Journal Editors (ICMJE) announced that their journals would not publish reports of trials unless they had been registered. The ICMJE action
7304-546: The treatment of abdominal aortic aneurysm , which compared the older open aortic repair technique to the newer endovascular aneurysm repair device. An example of the latter are clinical trials on mechanical devices used in the management of adult female urinary incontinence . Similarly to drugs, medical or surgical procedures may be subjected to clinical trials, such as comparing different surgical approaches in treatment of fibroids for subfertility . However, when clinical trials are unethical or logistically impossible in
7392-501: The trial in the same way on similar subjects and that the data is comparable across all subjects. As a trial is designed to test hypotheses and rigorously monitor and assess outcomes, it can be seen as an application of the scientific method , specifically the experimental step. The most common clinical trials evaluate new pharmaceutical products, medical devices, biologics , diagnostic assays , psychological therapies , or other interventions. Clinical trials may be required before
7480-516: The trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become approved drugs . Some clinical trials involve healthy subjects with no pre-existing medical conditions . Other clinical trials pertain to people with specific health conditions who are willing to try an experimental treatment. Pilot experiments are conducted to gain insights for design of
7568-489: The validity and value of the scientific evidence base." Since 2007, the International Committee of Medical Journal Editors ICMJE accepts all primary registries in the WHO network in addition to clinicaltrials.gov. Clinical trial registration in other registries excluding ClinicalTrials.gov has increased irrespective of study designs since 2014. Various studies have measured the extent to which various trials are in compliance with
7656-476: Was due to the inoculation or some other factor. Similar experiments performed by Edward Jenner over his smallpox vaccine were equally conceptually flawed. The first proper clinical trial was conducted by the Scottish physician James Lind . The disease scurvy , now known to be caused by a Vitamin C deficiency, would often have terrible effects on the welfare of the crew of long-distance ocean voyages. In 1740,
7744-664: Was probably the most important motivator for trial registration, as investigators wanted to reserve the possibility that they could publish their results in prestigious journals, should they want to. In 2007, the Food and Drug Administration Amendments Act of 2007 (FDAAA) clarified the requirements for registration and also set penalties for non-compliance (Public Law 110-85. The Food and Drug Administration Amendments Act of 2007 [1] . The International Committee of Medical Journal Editors (ICMJE) decided that from July 1, 2005 no trials will be considered for publication unless they are included on
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